Manic-depressive illness is known since the era of Hippocrates (460–357 BC), Galen (131–201 AD) and Areteus from Kappadokia, and is described in ancient medical texts. Some authors believe that King Saul was also suﬀering from this disease and David used to relieve his depression by playing music for him. The ancient Greeks and Romans coined the terms "melancholia" and "mania." Hippocrates was the first to describe melancholia which is the Greek word for "black bile" and simultaneously postulated a biochemical origin according to the scientific frame of that era, linking it to Saturn and the autumn. Mania was described as madness with elevated mood but it included a broad spectrum of excited psychotic states the way we understand them today. Soranus was the first to describe mixed states. Aretaeus of Cappadocia (2nd century AD) is considered to be the one who strongly connected melancholia with mania and made a description of manic episodes very close to the modern approach, including psychotic features and seasonality. Another interesting element in the theories that emerged during antiquity was the concept of temperament which was originally based on harmony and balance of the four humors, of which the sanguine humor was considered to be the healthiest but also predisposing to mania. The melancholic temperament was linked to black bile and was considered to predispose to melancholia. Since the time of Aristotle (384–322 BC), the melancholic temperament was linked to creativity. During the 10th and 11th century AD the Arab scholars dominated (Ishaq Ibn Imran, Avicenna and others). In 1621 Robert Burton wrote the first English-speaking text on the field of mood disorders "The Anatomy of Melancholy." Later, the works of Jean-Philippe Esquirol (1772-1840), Benjamin Rush (1745–1813), Henry Maudsley (1835–1918), Jean-Pierre Falret (1794-1870) and Jules Gabriel Francois Baillarger (1809-1890) established the connection between depression and mania. Finally, Emil Kraepelin (1856–1926) established manic-depressive illness as a nosological entity (and separated it from schizophrenia) on the basis of heredity, longitudinal follow-up and a supposed favorable outcome. Recent research data has reshaped our definition and understanding of bipolar and other mood disorders. Today the suboptimal outcome of mood disorders is well documented, especially in relationship to younger age of onset and to alcohol and substance abuse. Suicide is another major concern since up to 75% of patients who commit suicide suﬀer from some type of mood disorder. Recently the World Health Organization (WHO) has ranked neuropsychiatric disorders as one of the most disability inducing causes world-wide, more disabling than cancer and cardiovascular diseases, and equal to injuries from all causes (World Health Organization,2003). Aﬀective disorders combined are the most disabling neuropsychiatric conditions and one of the 4 leading disability causes.
PhenomenologyEpidemiology DSM-IV-TR unipolar major depressive disorder (U-MDD) is reported to be the most common mood disorder (Weissman et al. 1996). The overall current prevalence of MDD is estimated to be 4.7% for males and 6% for females and the annual incidence is around 1.59%. Depression of any type may aﬄict 10-25% of females and 5-12% of males at some time during their lives with the rates varying widely and depending on ethnic background, type of residential area, gender, age, social support and general somatic health status. The results of the US Epidemiologic Catchment Area (ECA) study suggest that disabling mood disorders aﬀect as high as 5-8% of the general population and that if milder depression is included then the lifetime prevalence increases to 17% (National Comorbidity Study -NCS). When subclinical mood states are included, it is reported that one third of the general population will be aﬀected (Dryman & Eaton, 1991; Eaton, Dryman, Sorenson, & McCutcheon, 1989; Eaton, Kramer et al. 1989). In spite of treatment, disability rates are high and suicide occurs in about 15% of patients, especially in men. Conversely, a significant proportion of suicide victims suﬀer from some kind of depressive state (Parkar, Dawani, & Weiss, 2006; Seguin et al. 2006; Zonda, 2006). For some people depression is a single episode in life but around half of those experiencing an episode will experience more in the future, and the likelihood after the second episode is to experience a third episode within a decade or so. One third of patients will recover within the first 2-3 months, another third will need 6-8 months and around 15% of patients will not have recovered after 2 years, and they are likely to develop a chronic course (Kruijshaar et al. 2005; Patten & Lee, 2004, 2005; Patten, 2006; Patten et al. 2006; Patten, 2007; Waraich, Goldner, Somers, & Hsu, 2004; Wulsin, Vaillant, & Wells, 1999). The epidemiological data concerning the risk factors for MDD is rich but inconclusive. Women are twice as likely as men to experience an episode of MDD (Coryell, Endicott, Andreasen, & Keller, 1985; Kessler, McGonagle, Swartz, Blazer, & Nelson, 1993; Tennant, 1985; Weissman et al. 1988) and age plays a complex role (Koeniq, Meador, Cotlen, & Blazer, 1988). MDD has an average age of onset between 20 and 40 years while bipolar disorder may appear more frequently in the early 20’s (Weissman et al. 1988). The eﬀect of socioeconomic status is weak if it exists at all (Hollingshead & Redlich, 2007). Marital status appears to be one of the most consistent risk factors for MDD with recently widowed, separated and divorced persons being at higher risk, and single and married persons at lower risk. A family history of MDD, especially in first-degree relatives, constitutes a major risk factor along with family history of suicide and alcoholism. Early childhood abuse per se may be related to increased neuroendocrine stress reactivity, which is further enhanced when additional trauma is experienced in adulthood (Heim et al. 2002). Some personality features (introversion, worry, dependency and interpersonal sensitivity) as well as social stressors and social support also constitute risk factors (Farmer et al. 2001; Iacovides, Fountoulakis, Fotiou, & Kaprinis, 2002; Paykel, 1994, 2001a, 2001b). Life events (especially loss and bereavement), chronic stress (financial, family and interpersonal diﬃculties), and daily hassles as well as routine changes even due to positive events (e.g., change in residency due to promotion at work) all constitute risk factors (Fotiou, Fountoulakis, Iacovides, & Kaprinis, 2003; Rijsdijk et al.2001). In addition, it has been reported that adolescent life events predicted an increased risk for major depression diagnosis in early adulthood (Pine, Cohen, Johnson, & Brook, 2002) The conclusion from few available community-based studies suggested that younger age, low social class, negative and stressful life events linked to the family were associated with increased risk of new onset depression (Friis, Wittchen, Pfister, & Lieb, 2002). Originally it has been suggested that the classic manic depressive psychosis had a prevalence of around 1% (0.4-1.6%). However, today we know that the true prevalence depends on the definition, and to an extent, the sub-threshold bipolar cases and pseudo-unipolar patients. In addition, personality disorders (PDs), especially borderline personality disorder, are included under the umbrella of the bipolar spectrum or under unipolar depression. Another open question is whether the avoidant and the dependent PDs constitute real PDs or instead are residuals of a previously experienced major depressive episode. This is because these two PDs have been detected only in patient populations and not really in general population samples. DSM-IV-TR Bipolar disorder (BD) type I and type II have a combined prevalence rate of up to 3.7%. The literature on the lifetime prevalence of BD suggests an overall rate of 3-6.5% including a wider spectrum of bipolarity in comparison to the DSM-IV-TR definition (Acorn, 1993; Angst, 1998; Judd & Akiskal, 2003). As for other risk factors (Laursen, Munk-Olsen, Nordentoft, & Bo Mortensen, 2007), although younger age, marital status (separated/divorced) and negative life events have been suggested to play a role, perhaps the best proven risk factor is the genetic transmission of bipolar disorder, which is much higher than that of MDD. Clinical symptoms and classification The onset of mood episodes can be acute or insidious, and emerge from a low-grade, intermittent, and protracted mood substrate which can resemble a dysthymic or cyclothymic state or even personality features (Fogel, Eaton, & Ford, 2006). These mood states can also prevail during the inter-episode period and may give rise to low quality of life, interpersonal conflicts and significant global disability. Furthermore, these subthreshold disorders are quite frequent in the families of patients (Shankman, Klein, Lewinsohn, Seeley, & Small, 2008). Dysthymic and cyclothymic disorders are recognized by contemporary classification systems as separate diagnostic entities and often do not lead to the manifestation of a full blown mood episode. Dysthymic disorder corresponds largely to a chronic mild form of depression with a relatively stable social functioning. Bipolar disorders (previously called manic-depressive psychosis) consists of at least one hypomanic, manic, or mixed episode. Mixed episodes represent a simultaneous mixture of depressive and manic or hypomanic manifestations. Although a minority of patients experience only manic episodes, most bipolar disorder (BD) patients experience episodes of both polarity.The classical definition of BD suggests that this disorder is characterized by the presence and alteration of manic and depressive episodes with a return to premorbid level of functioning between the episodes and a favorable outcome in comparison to schizophrenia (Kraepelin, 1921). Today we know that this is not always the case (Tohen, Waternaux, & Tsuang, 1990). The Kraepelinian concept largely corresponds to BD type I (BD-I) according to DSM-IV-TR (American Psychiatric Association, 2000). Typically, BD-I starts before the age of 40. Frequently the correct diagnosis is made after several years because the first episode is psychotic-like or depressive and the diagnosis is only evident after a manic or mixed episode emerges. Another type, BD-II is oﬃcially recognized as a bipolar illness subtype and it is characterized by the presence of hypomanic instead of manic episodes. However, it is important to note that according to DSM-IV-TR (American Psychiatric Association, 2000) hypomania is defined mainly in terms of a shorter duration of the episode. BD-II is more prevalent than BD-I disorder. An additional complicating factor for diagnosis is that patients usually experience hypomania as a recovery from depression and almost always as a pleasant ego-syntonic mood state. Depressive episodes are considered to be the second diagnostic pillar of BD. However, in contrast to manic episodes which lead to the diagnosis of BD immediately, depressive episodes pose a dilemma to the clinician regarding whether or not he or she faces a unipolar depression or a BD. This is an important dilemma to solve since the treatment of these disorders diﬀer. However, it has been estimated that more than half of patients originally manifesting a depressive episode will turn out to have BD in the next 20 years (Angst, Sellaro, Stassen, & Gamma, 2005). Unipolar-depressed patients who later "convert" to BD over time, as well as patients with bipolar depression manifest more frequently "atypical" features of depression (hypersomnia, hyperphagia, leaden paralysis, long term interpersonal rejection sensitivity, psychomotor retardation, psychotic features, pathological guilt and mood lability)(Perugi et al. 1998). BD patients also tend to have earlier age of onset, more prior episodes of depression, shorter depressive episodes, and family history of BD (Akiskal & Benazzi, 2008; Mitchell, Goodwin, Johnson, & Hirschfeld, 2008). Family history of BD is a strong predictor of bipolarity even in children and adolescents (Geller, Fox, & Clark, 1994). DSM-IV-TR recognizes atypical features of depression (Davidson, Miller, Turnbull,& Sullivan, 1982; Fountoulakis, Iacovides, Nimatoudis, Kaprinis, & Ierodiakonou, 1999; Thase, 2007). This depressive subtype includes the presence of personality-like features such as long-term interpersonal rejection sensitivity, and somatic symptoms such as reverse vegetative signs, hypersomnia, increased appetite, weight gain and leaden paralysis. There is strong evidence linking atypical depression to BD-II (Akiskal & Benazzi, 2005). Mixed episodes are also considered to be part of the BD picture, and according to DSM-IV-TR are defined as the co-existence of both depressive and manic symptoms to the extent that the criteria for both a manic and a depressed episode are fulfilled (Akiskal & Benazzi, 2004). Alterations in mood characterize several other DSM disorders which have a bipolar character. These include cyclothymic disorder and borderline personality disorder. However, there is a constellation of types of aﬀective episodes which are not part of the oﬃcial classification and they are so prevalent in real life clinical practice that many authors consider them to be the rule rather than the exception. Sometimes there is a mixture of manic and depressive symptoms in a combination which does not fulfill the specific DSM criteria for a manic, depressive or mixed episode. Therefore, the only possible diagnosis is that of a Not-Otherwise-Specified (NOS) mood episode (Akiskal, 1996; Akiskal et al. 1998). Often manic symptoms can go unnoticed by the clinician because instead of being hyper-thymic, the mood is irritable and is diluted in the presence of depressed thought content and suicidal ideation. Such a presentation may lead the clinician to the diagnosis of anxious or agitated depression, or worse, of a personality disorder, instead of a mixed or mixed-NOS mood episode. Frequently, this irritable mood can result in aggressive behavior especially if confronted or rejected while having grandiose or paranoid delusions. These patients may be the most aggressive seen in the emergency room (Maj, Pirozzi, Magliano, & Bartoli, 2003; Sato, Bottlender, Kleindienst, & Moller, 2005). There is evidence that an excited/irritable state can develop when antidepressants, especially dual action ones, are used. Many patients will not develop a classic manic episode in response; many will either develop a full blown mixed episode or more likely a DSM sub-threshold mixed-NOS episode with the presence of a small number of manic symptoms in combination with depression, especially agitation, and this state may persist and worsen if more aggressive antidepressant treatment is tried. Rapid cycling refers to patients suﬀering from at least 4 mood episodes in a year. It seems that females are more often rapid-cyclers as well as higher social class subjects. In essence, these patients tend to be symptomatic most of their life and are considered to be refractory to lithium. The diagnosis may elude for prolonged periods of time and the patients can receive the diagnosis of a personality disorder or cyclothymia. Treatment of rapid cycling is based on a complex, delicate and diﬃcult to design multiple pharmacotherapy which includes atypical antipsychotics, anticonvulsants and even antidepressants, although the latter are believed to induce rapid cycling (Bauer et al. 1994). Psychotic features are common in bipolar patients and may include delusions or hallucinations of any type. They can either be mood congruent or mood incongruent. In order to make the diagnosis of schizoaﬀective disorder according to DSM-IV-TR there must be a psychotic episode in the absence of prominent mood symptoms. However, according to ICD-10 this diagnostic boundary is vague and diﬀerential classification is often diﬃcult. Alcohol and substance abuse are very common problems in BD. Drug abuse may precipitate an earlier onset of BD-I in those who already have a familial predisposition for mania. Alcohol abuse may be present in more than half of patients. It seems that frequently this represents self-medication eﬀorts and abuse is particularly problematic during adolescence and early adulthood. At this age period substance and alcohol abuse may not only suppress symptoms but also enhance specific desired activities (e.g., high school performance, sex etc.). Alcohol abuse can cause further disinhibition and may cause the patient to manifest physical aggression especially towards the family, with "crimes of passion" being the most tragic result. BD patients tend to abuse stimulant drugs. Familial diathesis for mania is significantly associated with the abuse of alcohol and drugs and it is possible that there is a common familial-genetic diathesis for a subtype of BD-I, alcohol and stimulant abuse (Winokur et al.1998). The cognitive deficits of BD patients have not been studied adequately. However, in contrast to the early Kraepelinian concept for a favorable functioning outcome, recent studies suggest there is a significant degree of psychosocial impairment even when patients are euthymic and report that only a minority achieves complete functional recovery (Daban et al. 2006; Goldberg, Harrow, & Grossman, 1995a, 1995b; Keck et al. 1998; Martinez-Aran et al. 2007; Mur, Portella, Martinez-Aran, Pifarre, & Vieta, 2007; Strakowski et al. 1998). Cognitive impairment is reported to exist in both BD-I and BD-II patients, although more so in the BD-I group and this is true even during the euthymic period. The cognitive deficit can be worse during the manic phase but it is present during all phases of the illness (Dixon, Kravariti, Frith, Murray, & McGuire, 2004; Malhi, Ivanovski, Szekeres, & Olley, 2004). However, when compared to patients with schizophrenia, BD patients demonstrate a lesser degree of deficits, particularly concerning premorbid and current intelligence quotient and perhaps attention, verbal memory,verbal fluency and executive functions (Mur et al. 2007; Torrent et al. 2006). The pattern of the neurocognitive deficit implicates the prefrontal cortex and temporo-limbic structures, especially ventromedial areas as well as the amygdala and the hippocampus. Mood disorders are characterized by a constellation of symptoms and signs. The terms "depressed mood," "anhedonia" and "elevated mood" are central to the definition and diagnosis of these disorders. Mood • Euthymia refers to the normal range of mood, and the absence of any disorder. • Mourning refers to the experience of sadness as a consequence of a loss of a loved one. It includes, crying, sadness, preoccupation with the lost person and related memories. • Depressed mood means that the patient experiences a "negative" and unpleasant aﬀect, and in English and other western cultures and languages the words (or their linguistic equivalents) "depressed," "anguished," "mournful," "sad," "anxious," "blues" are used. The word "depressed" is increasingly used because of the higher information (partially because of the internet) the public has today on depression. The way patient uses describes this experience depends on his/her cultural and educational background, and can focus on bodily function or on existential and interpersonal dysphoria and diﬃculties. Somatic complaints are more prominent in milder cases usually seen in the primary care setting, particularly in patients with anxious depression. These patients were considered to suﬀer from "masked" depression. • Anhedonia refers to the inability to experience normal emotions. Frequently, patients with anhedonia are incapable of even feeling the depressed aﬀect and they can’t even cry. The patient abandons activities which in the past were a source of joy and gives up interest in life. Patients with more severe depression are indiﬀerent even concerning their children or spouse and isolate themselves. The diﬀerence from the flat (blunted) aﬀect seen in schizophrenia is that anhedonia is itself painful. As depression starts remitting, anhedonia is one of the first symptoms to remit. • Elevated mood refers to a state of elation, overconfidence, and enjoyment, with the person being cheerful, laughing and making happy and expressive gestures. It is not always pathological. • Euphoria refers to a pathologically too much elevated mood that is inappropriate to real events. It is considered to constitute the opposite pole of "depressed mood" with "normality" in the middle. Experiencing a euphoric mood is pleasant thus patients are reluctant to receive treatment. • Expansive mood is a condition with the patient expressing his/her feelings without restraint and control and behavior is usually colored by grandiose thoughts. • Emotional lability refers to unstable and rapidly changing emotions because of hyper-reactivity to environmental stimuli. It is not always pathological • Irritable mood is a state in which the person is easily annoyed by external stimuli and expresses anger and hostility at a low threshold. The presence of an irritable mood is often the cause for misdiagnosis of the patient, especially in combination with lability and mixed states. Psychomotor Disorder • Flight of ideas refers to an acceleration of the thinking processes, and it manifests itself in the form of rapid speech. Speech can be coherent and thoughts unusually sharp. However, when speed is excessively high, they both become incoherent and fragmented with content changing abruptly. Associations can be based on rhyme or chance perceptions. • Psychomotor acceleration is considered to be the hallmark of mania, characterized by excessive activity (which is goal directed, high energy and endurance) as well as rapid, pressured speech. • In comparison, psychomotor agitation also refers to a both mental and physical over-activity (pressured speech, restlessness, increased motor behavior) usually accompanied by a feeling of an inner turmoil or severe anxiety, with the intensity being so great that in spite of the fact that the patient has normal arousal, most if not all of this activity is purposeless. • Psychomotor slowing means that the patient is inert and slow, both physically and mentally, but this does not always have an eﬀect on overall performance although everything is done with much eﬀort • When psychomotor slowing is excessive, then psychomotor retardation appears and it includes reduction or disappearance of spontaneous motor activity, slumped posture and gaze, reduced and slow speech, and great fatigue. • Stupor appears in younger patients when the psychomotor retardation is so extreme that they are unable to perform even basic everyday tasks. In more severe cases, motoric immobility occurs. • Catatonia is defined as a complex condition which can include diverse symptoms and signs such as motoric immobility or on the contrary excessive purposeless motor activity not influenced by external stimuli, motiveless negativism, mutism, peculiar or stereotyped movements, mannerisms, grimacing and sometimes echolalia or echopraxia. • Fatigue is a common problem in all mental disorders but especially in mood disorders and includes feeling tired or weak, sleepy, and sometimes irritable. Neurocognitive Disorder The term "neurocognitive" is often used with reference to higher cognitive function, such as attention, concentration, memory, praxis etc., and in psychiatry in contrast to the term "cognitive" which often is used with reference to the thought content or style and relates to cognitive therapy. Bipolar patients constitute a clinically heterogeneous group. However, they seem to perform poorly on most neuropsychological tests in comparison to healthy controls. They seem to suﬀer from deficits especially related to attention, inhibitory control, spatial working memory, semantic verbal fluency, verbal learning and memory, and maybe executive function (especially when considering the more severe and psychotic end of the bipolar spectrum). Verbal memory and probably executive function impairments may represent a trait rather than a state marker (Martinez-Aran et al. 2007; Martinez-Aran et al. 2008). In extreme cases, neurocognitive disorder is so severe, especially in elderly patients that the picture resembles that of a dementing disease, thus is called "pseudodementia." However, it seems that at least half of these patients do in fact suﬀer from a dementing process at its early stages and later they manifest a formal dementia syndrome (Alexopoulos, Meyers, Young, Mattis, & Kakuma, 1993; Alexopoulos, Young, & Meyers, 1993; Bajulaiye & Alexopoulos, 1994; Reifler, 2000; Saez-Fonseca, Lee, & Walker, 2007) If one looks at the problem from another point of view, depression with mild cognitive disorder may be either the first manifestation or a risk factor for the development of dementia, especially when combined with a family history of dementia (Tsolaki, Fountoulakis, Chantzi, & Kazis, 1997; VanOjen & Hooijer, 1995; VanOjen, Hooijer, & . , 1995). Thought Disorder • Depressive thought content: depressed patients are characterized by a negative evaluation of the self, the world, and the future (the negative cognitive triad). In this frame, the depressive thought content includes pessimism, low self-esteem and low self-confidence, ideas of loss, deprivation and guilt, helplessness and hopelessness, and ultimately thoughts of death and suicide. The extent to which this negative way of thinking is primary or secondary is a matter for debate. • Clang association: refers to the condition when the patient’s thoughts association and subsequently the speech are directed by the sound of a word rather than by its meaning. Therefore, words are not connected in a logical way and punning and rhyming serve as the drive. • Thoughts of guilt concern self-reproach, self accussation and feeling the need for punishment. Thoughts and feelings of guilt are to largely normal and they can appear during a mood disorder because of the disability the disorder causes and the inability of the patient to fulfill his/her obligations towards significant others. In this frame patients may also feel shame. However, when the intensity and the content is excessive or even inappropriate then thoughts of guilt should be considered to be part of the symptoms and in more severe cases these thoughts may take on a delusional character. • Thoughts of death are particularly important because they may eventually lead to suicidal behavior. The common belief that inquiring about such thoughts provokes suicidal behavior has no scientific basis. On the contrary, patients are often relieved this way. These thoughts include thoughts that the person will die and often the wish to die in some way so as to leave the suﬀering behind; this way they lead to suicidal ideation. • Suicidal ideation refers to specific thoughts of killing oneself. It has many diﬀerent forms, ranging from indirect expression (e.g., a wish not to wake up, or to die from a disease or an accident), to suicidal obsessions (urges or impulses to destroy oneself) and finally to elaborate planning of suicide. Some patients behave in a passive self-destructing way (e.g., careless driving or walking) while others plan their death in detail leaving notes and making sure no help will come on time. • Manic thinking is excessively positive and optimistic. It is characterized by inflated self-esteem, grandiose sense (concerning importance, power, knowledge, or identity), over-confidence and sense of high achievements and abilities. Manic patients are refractory to explanations, confrontation, and to a significant extent they lack self-examination and insight; because of this lack of insight, mania nearly always, sooner or later acquires a delusional character. Psychotic Symptoms Psychotic features include delusions and hallucinations and both can be mood congruent or non-congruent depending on their content. Mood congruent psychotic features include those entirely consistent with the thought content (either manic or depressive) while mood incongruent are largely unrelated to it. Psychotic features are not uncommon in mood disorders, especially in bipolar disorder and delusions are relatively more common than hallucinations. • Mood-congruent depressive delusions: often depressed thoughts can acquire a delusional severity and delusions congruent with depressive mood appear. Their content concerns inappropriate or over-exaggerated thoughts of guilt, sin, worthlessness, poverty and somatic health. Delusions concerning persecution and jealousy, although seemingly non-congruent, can also be mood congruent if they can be explained by, or strongly related to, thoughts of sin, guilt, jealousy or worthlessness. This kind of delusional thought makes a parent kill his/her family so as to save them from moral or physical corruption and then he/she commits suicide. • Nihilistic delusions (Cotard delusion or Cotard's syndrome, negation delusion are related to depressive mood and concern the delusional belief that all or parts of the patient’s body are missing or rotten or decomposing, their internal organs are rotten or solidifying or are actually dead; the world and everything related to it have ceased to exist. • Mood-congruent manic delusions: during manic episodes usually the thought content becomes delusional and includes delusions of exceptional mental and physical fitness or special talents. It may also include delusions of wealth, some kind of grandiose identity or importance. Sometimes the delusion can be so excessive that the identity itself changes (e.g., the patient believes that he is the incarnation of a messiah or a prophet etc.) Delusions of reference and persecution are considered to be mood-congruent on the basis of the belief that jealousy of the others at their special abilities is the cause of problems. • Mood-incongruent delusions: various delusional ideas seemingly non-congruent (e.g., ideas of persecution or reference) can eventually be understood as arising from the grandiose sense of self and the belief of the patient that this importance causes the others to envy. However, sometimes there are delusions with no association to current mood (e.g., bizarre delusions without contextual relationship to mood). Sometimes a mixed mood episode can manifest itself with mood-incongruent delusions e.g., grandiose delusions in the presence of depressed mood. • Depressive mood-congruent hallucinations are hallucinations consistent with either a depressed (e.g., voices accusing or humiliating) or manic mood (e.g., voices praising). Depressive mood-congruent hallucinations have an unpleasant content and they cause significant additional distress to the patient. Sometimes they command the patient to commit suicide and even dictate the method. • Manic mood-congruent hallucinations: sometimes a manic mood causes such a vivid internal experience that the patient feels he/she can hear or see his/her own thoughts (e.g., hear hymns or live in the paradise). • Mood-incongruent hallucinations refer to hallucinations unrelated to the current mood state. • Insight: classically, depressive episodes are characterized by a fair degree of insight with the exception of the more severe psychotic cases. On the contrary, manic episodes are routinely characterized by a significant lack of insight and thus clinicians must routinely obtain basic information from significant others. This lack of insight may lead to refusal of treatment and to the need for involuntary admission to hospital. Somatic and Neurovegetative Symptoms Depressed patients often manifest changes in appetite, sleep and sexual functioning. Circadian rhythms are also disrupted. The classical notion of depression which is closer to melancholia includes reduction in all these functions; however, recently the "atypical" form of depression was described and this form includes an increase in these neurovegetative functions; that is overeating and oversleeping along with interpersonal rejection sensitivity which is a "personality-like" feature. • Anorexia and weight loss: are considered to be reliable signs of depression. They can both be considered in the frame of a generalized inability to enjoy things (anhedonia). Weight loss is seen sometimes in paranoid patients who are afraid that food is poisoned and this should not be confused with anorexia and weight loss in the frame of depression. Weight loss is also frequent in cases of malignant disease so a full medical investigation should accompany any patient with changes in appetite or weight. • Weight gain has been, relatively recently, recognized as a depressive feature and could be the result of overeating, decreased activity, or both. Apart from its devastating eﬀect on the self-confidence and self-image, it can worsen the general somatic health especially in patients that become obese and suﬀer from metabolic syndrome. • Insomnia is one of the hallmarks of depression and one of its most disturbing features. There are many types of insomnia that is, diﬃculty falling asleep (initial insomnia), multiple awakenings during the night (middle insomnia) or early morning awakening (terminal insomnia). Insomnia prolongs the depressive agony round the clock. Some patients try to self-medicate and solve the problem by alcohol or drug abuse (sedatives or hypnotics) but both eventually worsen the problem, partially because of tolerance and dependence problems and partially because they both further destroy the architecture of sleep. Unipolar depressed patients tend to exhibit insomnia stereotypically episode after episode and characteristically, in spite of extreme fatigue, they rarely oversleep. • Hyposomnia: the term suggests a decreased need for sleep. That is, the patient feels energetic on awakening even though he slept for short periods. Some patients feel fresh and energetic even though he/she haven’t slept for days. This condition is usually seen during manic episodes and sometimes it heralds the beginning of such an episode. • Hypersomnia: some patients, especially younger ones and females, often sleep too much and find it diﬃcult to get up from the bed in the morning. Along with the other atypical features it is considered to be a marker for an underlying bipolar illness even in cases where no other bipolar feature is present. This condition should be diﬀerentially diagnosed from a number of medical conditions including narcolepsy and the Klein-Levin syndrome. In spite of prolonged sleep, depressed patients are characteristically tired in the morning, meaning that even prolonged sleep is not refreshing for them. The change in the pattern of sleep disruption with insomnia alternating with hypersomnia or hyposomnia suggests the presence of a bipolar illness rather than a unipolar depression. • Circadian dysregulation: although many circadian functions can be disrupted in depressed patients, mainly the disturbance of sleep rhythms has been adequately studied. This disturbance includes deficits in delta sleep and more intense rapid eye movement (REM) activity during the first third of the night. A marked shortening of REM latency (that is the time from the onset of sleep to the first REM period) is considered to be characteristic for depression of any type, and seen even in remitted depressive patients and their healthy relatives. • Seasonality: seasonal (especially autumn-winter) emergence or worsening of depression has been recognized since antiquity and mood has been related to the period of the year. Most patients seem to experience increased energy and activation during spring and the opposite during the fall and winter. Usually patients with strong seasonality also have reverse neurovegetative symptoms (fatigue, crave sugars, overeat and oversleep). In some patients seasonality is so concrete and important that modern classification includes a seasonal pattern for mood disorders. • Sexual dysfunction: depressed patients classically report a decreased sexual desire and activity while additionally some women manifest a temporary interruption of their menses. Sexual dysfunction especially in females can lead to marital conflict and a psychody-namic/psychotherapeutically oriented therapist can mistakenly ascribe depression to the marital conflict with profound negative eﬀects on the therapeutic outcome. Treating the sexual dysfunction or its consequences and leaving depression untreated is not uncommon and includes even surgical or unusual therapeutic interventions. An additional problem is that treatment with antidepressants often has sexual dysfunction as an adverse eﬀect. The recent emergence of agents that treat impotence (e.g., sildenafil, tadalafil) could add a new method to treat this problematic symptom but this should never move the focus of treatment away from depression. • Increased sexual desire and activity is typical for manic episodes, but also a subgroup of depressed patients may manifest increased sexual drive or activity and usually they also manifest other atypical or "reversed" features. Therefore, if seen in the frame of depression it heralds the presence of a depressive mixed episode. The increased sexual appetite usually leads to sexual indiscretion accompanied by a risky sexual life, often leading to marital problems, multiple separations or divorces, alcohol and drug abuse, gambling and sexually transmitted diseases like AIDS Behavioral Disorder • Logorrhea refers to pressured, excessive and not always coherent speech, which is often uncontrollable. It is observed during manic episodes. Speech can be completely incomprehensible, with destroyed syntax and loose associations, often posing diagnostic dilemmas (e.g., from stroke). Other similar terms used are tachylogia, verbomania, volubility. • Impulsive behavior: during mood episodes, either manic, depressive or mixed, patients tend to exhibit impulsive behavior. Especially during manic episodes they tend to be impulsive, disinhibited, and meddlesome. They are intrusive with increased involvement with others, poor social judgment and engage in a variety of activities without control or restraint (including aggression, sex, gambling, drug and alcohol abuse, spending, making gifts, risk taking, travelling etc.) Impulsive behavior is symptom that causes most problems and especially financial and interpersonal. In some cases even suicide may be acted on an impulsive basis. The terms "endogenous depression," "neurotic depression," "anxious depression," "involutional melancholia," "psychotic depressive reaction" are not included in modern classification systems for a variety of reasons. The term "neurasthenia" is maintained in ICD-10 but its meaning is vague. It seems that the psychotic melancholic subtype is the most stable type of depression repeating itself across episodes (Coryell et al. 1994). Almost a third of all major depressive episodes do not recur and it seems that recurrent depression is more familial with on average 6 months episode duration and a varying inter-episode interval length. A significant proportion of patients remain symptomatic and disabled, many of them suﬀering from subsyndromal depression (Judd et al. 1998). Around 15% develops psychotic features Comorbidity Large epidemiological studies and clinical experience suggest that mood disorders either co-exist or overlap considerably with anxiety disorders. Anxiety disorders can occur during a depressive episode, may be a precursor to it, or may appear during the future course of a mood disorder. Several authors suggest there is a common diathesis connecting mood and anxiety disorders with more recent data suggesting a strong link between BD-II and panic, obsessive-compulsive disorder, and social phobia. All mood disorders but especially bipolar disorder are highly likely be comorbid with alcohol and drug (mainly stimulants) abuse, usually in the frame of a self-treatment eﬀort from the side of the patient (Winokur et al. 1998). Somatic illness frequently co-exists with depression and anxiety and the mood disorder has a profound negative impact on the outcome of the somatic illness. The therapist should also suspect clinical depression in all patients who refuse to participate in medical care. Classification The International Classification of Diseases, 10th version (ICD-10) includes sets of criteria for mood disorders, which are used throughout the world and constitute the oﬃcial method of reporting health statistics. They are overlapping with the Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) criteria; however, important diﬀerences do exist. The basis of the classification in both systems is the definition of the depressive and manic/hypomanic episodes. The two systems describe mood disorders as follows: In the ICD-10 the depressive episode is defined as follows: A. DEPRESSIVE EPISODE General criteria for a depressive episode: G1. The depressive episode should last for at least 2 weeks. G2. There have been no hypomanic or manic symptoms suﬃcient to meet the criteria for hypomanic or manic episode (F30._) at any time in the individual's life. G3. Most commonly used exclusion clause. The episode is not attributable to psychoactive substance use (F10-F19) or to any organic mental disorder (in the sense of F00-F09). F32: Depressive episode A. The general criteria for depressive episode (F32) must be met. B. At least two of the following three symptoms must be present: (1) depressed mood to a degree that is definitely abnormal for the individual, present for most of the day and almost every day, largely uninfluenced by circumstances, and sustained for at least 2 weeks; (2) loss of interest or pleasure in activities that are normally pleasurable; (3) decreased energy or increased fatigability. C. An additional symptom or symptoms from the following list should be present, to give a total of at least: four for mild (F32.0), six for moderate (F32.1) and eight for severe (F32.2 or F32.3 - depending on psychotic symptoms)depressive episode: (1) loss of confidence or self-esteem; (2) unreasonable feelings of self-reproach or excessive and inappropriate guilt; (3) recurrent thoughts of death or suicide, or any suicidal behavior; (4) complaints or evidence of diminished ability to think or concentrate, such as indecisiveness or vacillation; (5) change in psychomotor activity, with agitation or retardation (either subjective or objective); (6) sleep disturbance of any type; (7) change in appetite (decrease or increase) with corresponding weight change. A fifth character may be used to specify the presence or absence of the "somatic syndrome": F32.x0 Without somatic syndrome F32.x1 With somatic syndrome F32.2: Without psychotic symptoms (only for severe depressive episode) F32.3: With psychotic symptoms (only for severe depressive episode) F32.3: Severe depressive episode with psychotic symptoms A. The general criteria for depressive episode (F32) must be met. B. The criteria for severe depressive episode without psychotic symptoms (F32.2) must be met with the exception of criterion D. C. The criteria for schizophrenia (F20.0-F20.3) or schizoaﬀective disorder, depressive type (F25.1), are not met. D. Either of the following must be present: (1) delusions or hallucinations, other than those listed as typically schizophrenic in criterion G1(1)b, c, and d for general criteria for F20.0-F20.3 (i.e., delusions other than those that are completely impossible or culturally inappropriate and hallucinations that are not in the third person or giving a running commentary); the commonest examples are those with depressive, guilty, hypochondriacal, nihilistic, self-referential, or persecutory content; (2) depressive stupor. A fifth character may be used to specify whether the psychotic symptoms are congruent or incongruent with mood: F32.30: With mood-congruent psychotic symptoms (i.e., delusions of guilt, worthless-ness, bodily disease, or impending disaster, derisive or condemnatory auditory hallucinations) F32.31: With mood-incongruent psychotic symptoms (i.e., persecutory or self-referential delusions and hallucinations without an aﬀective content) F32.8: Other depressive episodes: Episodes should be included here which do not fit the descriptions given for depressive episodes, but for which the overall diagnostic impression indicates that they are depressive in nature. Examples included fluctuating mixtures of depressive symptoms (particularly those of the somatic syndrome) with nondiagnostic symptoms such as tension, worry, and distress, and mixtures of somatic depressive symptoms with persistent pain or fatigue not due to organic causes (as sometimes seen in general hospital services). F32.9: Depressive episode, unspecified Somatic syndrome Some depressive symptoms are widely regarded as having special clinical significance and are here called "somatic" (terms such as biological, vital, melancholic, or endogenomorphic are used for this syndrome in other classifications). A fifth character may be used to specify the presence or absence of the somatic syndrome. To qualify for the somatic syndrome, four of the following symptoms should be present: (1) marked loss of interest or pleasure in activities that are normally pleasurable; (2) lack of emotional reactions to events or activities that normally produce an emotional response; (3) waking in the morning 2 hours or more before the usual time; (4) depression worse in the morning; (5) objective evidence of marked psychomotor retardation or agitation (remarked on or reported by other people); (6) marked loss of appetite; (7) weight loss (5% or more of body weight in the past month); (8) marked loss of libido. In The ICD-10 Classification of Mental and Behavioural Disorders: Clinical descriptions and diagnostic guidelines, the presence or absence of the somatic syndrome is not specified for severe depressive episode, since it is presumed to be present in most cases. For research purposes, however, it may be advisable to allow for the coding of the absence of the somatic syndrome in severe depressive episode. The DSM-IV-TR definition of the depressive episode is similar in essence to the ICD-10 definition; however there are some diﬀerences. The time duration of 2 weeks is the same, but the first set of criteria to be met (the equivalent of criterion B) includes only the first two, that is depressed mood and loss of pleasure and not decreased energy, and demands either of them to be present in contrast to ICD which demands two out of three. The list of depressive symptoms of DSM-IV-TR does not include "loss of confidence or self esteem" and demands five out of a total of nine to be present. There is a definition for "mild" (up to 6 symptoms) but the definition of "moderate" and "severe" episodes are based rather on global disability. Most criteria include a more explicit time and intensity description, e.g., "nearly every day." ICD-10 demands symptoms do not fulfill the diagnosis of a manic/hypomanic episode while DSM-IV-TR demands the same for a mixed episode, but in essence it is the exactly the same. DSM-IV-TR includes the need of a functional impairment and that symptoms are not better accounted by bereavement. Both systems accept the possibility of the presence of mood congruent or incongruent psychotic symptoms; however while the ICD-10 implies that specific psychotic symptoms are more or less pathognomonic of a schizophrenia-like psychosis (like hallucinations giving a running commentary), the DSM-IV-TR accepts all kind of psychotic experiences in the frame of a mood episode. This creates a profound diﬀerence in the way the two systems define the boundary between psychotic mood disorder and schizoaﬀective disorder, and define the latter in a very diﬀerent way. Another important diﬀerence between the two systems is that the ICD-10 defines the "somatic syndrome" while the DSM-IV-TR the "melancholic features." Both definitions are an attempt to include an "endogenous/melancholic-like" subgroup in the classification. It seems that the DSM-IV-TR definition is closer to this, while the ICD-10 definition includes too many anxiety and non-specific symptoms. Also the DSM-IV-TR includes the "atypical features" on the basis of mood reactivity, interpersonal rejection sensitivity and reversed neurovegatative symptoms. It seems that the DSM approach has higher reliability (Fountoulakis et al. 1999). Also catatonic features and postpartum onset are distinct specifiers for DSM. B. MANIC EPISODE F30.0: Hypomania A. The mood is elevated or irritable to a degree that is definitely abnormal for the individual concerned and sustained for at least 4 consecutive days. B. At least three of the following signs must be present, leading to some interference with personal functioning in daily living: (1) increased activity or physical restlessness; (2) increased talkativeness; (3) distractibility or diﬃculty in concentration; (4) decreased need for sleep; (5) increased sexual energy; (6) mild overspending, or other types of reckless or irresponsible behavior; (7) increased sociability or overfamiliarity. C. The episode does not meet the criteria for mania (F30.1 and F30.2), bipolar aﬀective disorder (F31._), depressive episode (F32._), cyclothymia (F34.0), or anorexia nervosa (F50.0). D. Most commonly used exclusion clause. The episode is not attributable to psychoactive substance use (F10-F19) or to any organic mental disorder (in the sense of F00-F09). F30.1: Mania without psychotic symptoms A. Mood must be predominantly elevated, expansive, or irritable, and definitely abnormal for the individual concerned. The mood change must be prominent and sustained for at least 1 week (unless it is severe enough to require hospital admission). B. At least three of the following signs must be present (four if the mood is merely irritable), leading to severe interference with personal functioning in daily living: (1) increased activity or physical restlessness; (2) increased talkativeness ("pressure of speech"); (3) flight of ideas or the subjective experience of thoughts racing; (4) loss of normal social inhibitions, resulting in behavior that is inappropriate to the circumstances; (5) decreased need for sleep; (6) inflated self-esteem or grandiosity; (7) distractibility or constant changes in activity or plans; (8) behavior that is foolhardy or reckless and whose risks the individual does not recognize, e.g., spending sprees, foolish enterprises, reckless driving; (9) marked sexual energy or sexual indiscretions. C. There are no hallucinations or delusions, although perceptual disorders may occur (e.g., subjective hyperacusis, appreciation of colors as especially vivid). D. Most commonly used exclusion clause. The episode is not attributable to psychoactive substance use (F10-F19) or to any organic mental disorder (in the sense of F00-F09). F30.2: Mania with psychotic symptoms A. The episode meets the criteria for mania without psychotic symptoms with the exception of criterion C. B. The episode does not simultaneously meet the criteria for schizophrenia (F20.0-F20.3) or schizoaﬀective disorder, manic type (F25.0). C. Delusions or hallucinations are present, other than those listed as typically schizophrenic in criterion G1(1)b, c and d for F20.0-F20.3 (i.e., delusions other than those that are completely impossible or culturally inappropriate, and hallucinations that are not in the third person or giving a running commentary). The commonest examples are those with grandiose, self-referential, erotic, or persecutory content. D. Most commonly used exclusion clause. The episode is not attributable to psychoactive substance use (F10-F19) or to any organic mental disorder (in the sense of F00-F09). F30.20: With mood-congruent psychotic symptoms (such as grandiose delusions or voices telling the individual that he or she has superhuman powers) F30.21: With mood-incongruent psychotic symptoms (such as voices speaking to the individual about aﬀectively neutral topics, or delusions of reference or persecution) F30.8: Other manic episodes F30.9: Manic episode, unspecified The DSM-IV-TR definition of the manic episode does not include a specific criterion for sexual behavior and condenses three ICD-10 criteria (#1, 4 and 8) into two. In essence the definitions are almost identical also requiring the same time duration. However, while in the ICD-10 the definition of hypomania requires a diﬀerent set of criteria, in DSM-IV-TR hypomania diﬀers from mania only in the duration which is at least 4 days and in the criterion suggesting a milder impairment in comparison to mania. Maybe the ICD-10 definition includes some cases which could be subthreshold for DSM-IV-TR. The DSM-IV-TR includes criteria concerning the impairment severity and suggests that hypomania is a milder condition which however, is clearly diﬀerent from the normal condition of the person and is observable by others. It also includes a note that hypomania caused by any somatic antidepressant treatment should not count towards the diagnosis of a bipolar disorder. C. MIXED EPISODE F38.0: Mixed aﬀective episode A. The episode is characterized by either a mixture or a rapid alternation (i.e., within a few hours) of hypomanic, manic, and depressive symptoms. B. Both manic and depressive symptoms must be prominent most of the time during a period of at least 2 weeks. The DSM-IV-TR definition demands the patient fulfills for at least 1 week the criteria both for a major depressive and a manic episode, thus this definition is far more rigid. Taking into account the fact that a significant number of patients might fulfill the ICD-10 criteria for mixed episode, but not the respective DSM-IV-TR definition, this diﬀerence in classification could make classifications by the two systems to deviate significantly. Both systems classify "ultra-rapid cycling" as mixed episodes. On the basis of the existence or not of hypomanic, manic, depressive and mixed episodes and accompanying features and longitudinal course, the ICD-10 recognizes the following disorders: DISORDERS F33: Recurrent depressive disorder • current episode mild, with/without somatic syndrome • current episode moderate, with/without somatic syndrome • current episode severe with/without mood-congruent/incongruent psychotic symptoms • currently in remission • Other recurrent depressive disorders • Recurrent depressive disorder, unspecified F31: Bipolar aﬀective disorder • current episode hypomanic • current episode manic with/without mood-congruent/incongruent psychotic symptoms • current episode moderate or mild depression with/without somatic syndrome • current episode severe depression with/without mood-congruent/incongruent psychotic symptoms • current episode mixed • currently in remission • Other bipolar aﬀective disorders • Bipolar aﬀective disorder, unspecified F34.0: Cyclothymia A. There must have been a period of at least 2 years of instability of mood involving several periods of both depression and hypomania, with or without intervening periods of normal mood. B. None of the manifestations of depression or hypomania during such a 2-year period should be suﬃciently severe or long-lasting to meet criteria for manic episode or depressive episode (moderate or severe); however, manic or depressive episode(s) may have occurred before, or may develop after, such a period of persistent mood instability. C. During at least some of the periods of depression at least three of the following should be present: (1) reduced energy or activity; (2) insomnia; (3) loss of self-confidence or feelings of inadequacy; (4) diﬃculty in concentrating; (5) social withdrawal; (6) loss of interest in or enjoyment of sex and other pleasurable activities; (7) reduced talkativeness; (8) pessimism about the future or brooding over the past. D. During at least some of the periods of mood elevation at least three of the following should be present: (1) increased energy or activity; (2) decreased need for sleep; (3) inflated self-esteem; (4) sharpened or unusually creative thinking; (5) increased gregariousness; (6) increased talkativeness or wittiness; (7) increased interest and involvement in sexual and other pleasurable activities; (8) overoptimism or exaggeration of past achievements. Note. If desired, time of onset may be specified as early (in late teenage or the 20s) or late (usually between age 30 and 50 years, following an aﬀective episode). F34.1: Dysthymia A. There must be a period of at least 2 years of constant or constantly recurring depressed mood. Intervening periods of normal mood rarely last for longer than a few weeks, and there are no episodes of hypomania. B. None, or very few, of the individual episodes of depression within such a 2-year period should be suﬃciently severe or long-lasting to meet the criteria for recurrent mild depressive disorder (F33.0). C. During at least some of the periods of depression at least three of the following should be present: (1) reduced energy or activity; (2) insomnia; (3) loss of self-confidence or feelings of inadequacy; (4) diﬃculty in concentrating; (5) frequent tearfulness; (6) loss of interest in or enjoyment of sex and other pleasurable activities; (7) feeling of hopelessness or despair; (8) a perceived inability to cope with the routine responsibilities of everyday life; (9) pessimism about the future or brooding over the past; (10) social withdrawal; (11) reduced talkativeness. Note. If desired, time of onset may be specified as early (in late teenage or the 20s) or late (usually between age 30 and 50 years, following an aﬀective episode). F34.8: Other persistent mood [aﬀective] disorders This is a residual category for persistent aﬀective disorders that are not suﬃciently severe or long-lasting to fulfill the criteria for cyclothymia (F34.0) or dysthymia (F34.1) but that are nevertheless clinically significant. Some types of depression previously called "neurotic" are included here, provided that they do not meet the criteria for either cyclothymia (F34.0) or dysthymia (F34.1) or for depressive episode of mild (F32.0) or moderate (F32.1) severity. F34.9: Persistent mood [aﬀective] disorder, unspecified F38: Other mood [aﬀective] disorders There are so many possible disorders that could be listed under F38 that no attempt has been made to specify criteria, except for mixed aﬀective episode (F38.00) and recurrent brief depressive disorder (F38.10). Investigators requiring criteria more exact than those available in Clinical descriptions and diagnostic guidelines should construct them according to the requirements of their studies. F38.10: Recurrent brief depressive disorder A. The disorder meets the symptomatic criteria for mild (F32.0), moderate (F32.1), or severe (F32.2) depressive episode. B. The depressive episodes have occurred about once a month over the past year. C. The individual episodes last less than 2 weeks (typically 2–3 days). D. The episodes do not occur solely in relation to the menstrual cycle. F38.8: Other specified mood [aﬀective] disorders This is a residual category for aﬀective disorders that do not meet the criteria for any other categories F30-F38.1 above. There are significant diﬀerences in the way the two systems conceptualize bipolar illness apart from the diﬀerences that occur because of diﬀerent definitions of mood episodes. The DSM-IV-TR separates Bipolar I (which includes manic episodes) and Bipolar II (which includes hypomanic but not manic episodes) disorders on the base of the longitudinal history of the disorder. On the contrary, the ICD-10 distinguishes them only concerning the "current episode" irrespective of past episodes. The greatest diﬀerence concerning cyclothymia is that ICD-10 demands the presence of 3 out of 8 depressive or manic symptoms during the downs and up, while the DSM-IV-TR refers only to depressive and hypomanic symptoms from the list of criteria for major depressive and hypomanic episodes without any threshold. On the contrary the separate lists of symptoms criteria suggested by the ICD-10 diﬀer significantly from the respected list for depressive episodes and hypomanic episodes and thus eventually the definitions of cyclothymia of the two classification systems diﬀer significantly. The definition of DSM-IV-TR concerning dysthymia diﬀers significantly from that of ICD-10 since it demands the presence of 2 out of 6 criteria in comparison to 3 out of 11 for ICD-10. The DSM-IV-TR criteria include appetite and weight changes and hypersomnia and not only insomnia. The ICD-IV-TR largely duplicates criteria although depending on the definition overlapping is not complete always (e.g., "depressed" and "frequent tearfulness;" "pessimism" and "hopelessness"). The DSM-IV-TR definition considers dysthymia to be a chronic mild form of depression while the ICD-10 stresses the cognitive and interpersonal impairment. Classification of mood disorders due to a somatic disease or substance abuse: F00-F09: Organic, including symptomatic mental disorders F06.3: Organic mood (aﬀective) disorder Organic manic disorder F06.31: Organic bipolar disorder F06.32: Organic depressive disorder F06.33: Organic mixed aﬀective disorder F06.6: Organic emotionally labile (asthenic) disorder F10-F19: Mental and behavioural disorders due to psychoactive substance use F1x.54: Predominantly depressive symptoms F1x.55: Predominantly manic symptoms F1x.56: Mixed Assessment Mood disorders should be diﬀerentially diagnosed from a number of other morbid conditions, both psychiatric and non-psychiatric. Several mental disorders including alcohol and substance use disorders, normal bereavement, depression in the frame of schizophrenia, anxiety disorders, personality disorders, dementia and a variety of general medical conditions that cause syndromes similar to depression should be diﬀerentiated from mood disorders. Also several drugs used for the treatment for a number of diseases might also cause depression. In general the prevailing opinion is that a missed diagnosis of mood disorder in favor of another mental diagnosis may mean that the patients does not receive proper treatment, which has serious consequences. Maybe the most important diﬀerential diagnosis should be made between mood and person-ality disorders. Since the state dependency of most personality features is well documented (Grilo et al. 2004; Grilo et al. 2005; Gunderson et al. 2004; McGlashan, 1986; McGlashan et al. 2005; Morey et al. 2004; Stone, 1993, 2005; Warner et al. 2004), clinicians should avoid putting this diagnosis in patients with an active mood disorder, even in cases this mood disorder is subthreshold. A dangerous stereotypical thinking leads clinicians to suggest that because a patient does not respond adequately to usual treatment the disorder is personality-based. This is especially problematic concerning subthreshold or non-classic mixed clinical pictures which are relatively refractory to treatment and cause despair to the therapist. Normal bereavement appears normally in persons experiencing the loss of a significant other and consists of several depressive symptoms during the first 1-2 years after the loss. But only around 5% will eventually progress to a depressive disorder. Normal bereavement is generally contrasted with depression because reactivity to the environmental stimuli is preserved, the disability if any is mild and no severe psychopathology (delusions or hallucination or true suicidal ideation) is present. Anxiety symptoms commonly occur in mood patients, including panic attacks, fears, and obsessions. Longitudinal data suggest that although the depressive symptoms tend to remit by passing the time, the anxiety symptoms persist. Because anxiety disorders rarely appear after the age of 40 for the first time, a late appearance of significant anxiety should be considered to be a sign of depression. Transient and periodic monosymptomatic phobic and obsessional states that do not fulfill criteria for a formal disorder as conceptualized in either classification system should also be considered as reflecting an underlying mood disorder and should be treated accordingly. Somatic complaints especially in depression might also reflect an underlying physical illness rather than a somatization mechanism. The somatic disorders most commonly related to depression are Multiple Sclerosis, Parkinson's disease, head trauma, epilepsy, sleep apnea, cerebral tumors, vascular encephalopathy, chronic fatigue syndrome, some collagen disorders like rheumatoid arthritis and lupus erythematosus and various neoplastic conditions like abdominal malignancies (especially in the pancreas) and disseminated carcinomatosis. Also there is a number of abnormal endocrine conditions including hypo- and hyperthyroidism, hyperparathyroidism, hypopituitarism, Addison's disease, Cushing's disease and diabetes mellitus, several infections like general paresis (tertiary syphilis), toxoplasmosis, influenza, vi-ral pneumonia, viral hepatitis, infectious mononucleosis and AIDS, and nutritional conditions like pellagra and pernicious anemia. A number of pharmacological agents used for the treatment of various diseases could cause depression or a depressive-like condition. These include a-methyldopa, anticholinesterase insecticides, cimetidine, cycloserine, indomethacin, mercury, phenothiazine antipsychotic drugs, reserpine, steroidal contraceptives, thallium, vinblastine and vincristine Withdrawal from agents like amphetamine, alcohol or sedative-hypnotics could also be the cause of depression. In geriatric patients the diﬀerentiation between depressive pseudodementia and degenerative dementia is vital and is done by the neuropsychological profile of the patient as well as from the clinical course which in pseudodementia cases includes an acute onset without prior cognitive disorder, a personal or family history of aﬀective illness, circumscribed memory deficits and an unstable cognitive dysfunction that can be reversed with proper coaching. The need for the diﬀerential diagnosis of mood disorders from the above mentioned conditions makes important for the clinician to obtain a variety of laboratory examination data including standard blood and biochemical tests, EEG, ECG, thyroid function tests and in depending on availability and cost even brain MRI and in late onset cases indices assessing malignancy. There are a large number of neuropsychological and psychometric tools available for the assessment of mood disorders and the clinician can choose which to use on the basis of his training and specific needs. However, a basic list includes the following tools: Psychometric Tools • Visual Analogue Scale (Rosenthal, Goldfarb, Carlson, Sagi, & Balaban, 1987): This is a very simple method, according to which, the examiner or the patient himself is asked to determine the quantity of the symptomatology on a bar 100 mm in length. One end of the bar is defined as "lack of depression" (0 mm) and the opposite one as "profound depression" (100 mm). The distance from the beginning (0 mm) is considered as the "degree" of depression. This method is has been in existence since 1921. A positive relationship between the subject’s ratings, the examiners’ opinion, and the score on the Beck Depression Inventory is reported. Today, it is considered somewhat outdated and not suitable for research purposes. • Hamilton Depression Rating Scale (HDRS) (Hamilton, 1960): This is the most widely known and used scale worldwide. It is examiner-rated. The basic scale includes 17 items, some of them assessing somatic symptoms, other assess anxiety or vegetative function and others could be contaminated by medication side eﬀects. Therefore although it is a comprehensive scale, its use of this scale in somatic patients or the elderly patients has some limitations. It also under-assesses atypical depressive patients. • Beck Depression Inventory (BDI-I) (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961): This is a widely used self-report scale that measures the thought content, or cognitive aspect of depression. It includes 21 items. Its properties when used in somatic patients or the elderly are less well known. A revised version (BDI-II) (Beck, Steer, Ball, & Ranieri, 1996) which is adjusted to modern classification is also available. • Zung Depression Rating Scale (ZDRS) (Zung, 1965): This is an old self-report scale which reflects an older concept of depression that dominated during the 60s, and might not produce reliable and valid results in somatic patients and geriatric populations. It also under-assesses atypical depressive patients. • Montgomery-Asberg Depression Rating Scale (MADRS) (Montgomery & Asberg, 1979): This instrument was the product of the need for scales with high sensitivity to changes produced by antidepressant medication. It is rated by an examiner. As a result, it includes only 10 items and almost no "somatic" symptomatology. A significant drawback of this scale is that its content is restricted to those symptoms responsive to medication at the time of the design of the scale, and therefore it does not represent a global assessment of depression. Another drawback is that it was developed for use in younger and somatically healthy patients. The content and method of development of the scale might make its application in somatic patients and elderly individuals problematic and its application in this population may lead to erroneous conclusions. • Geriatric Depression Scale (GDS) (Yesavage et al. 1982): It is the first scale especially designed for use in elderly populations. It is a self-report scale however, sometimes it is necessary to administer it through an interviewer. It exists in a 30-item and a 15-item form. It focuses mainly on the psychological concern of the patient and the way he/she perceives life, avoiding the assessment of somatic complaints. • Center for Epidemiological Studies-Depression Scale (CES-D) (Radloﬀ, 1977): It is a self-report instrument and one of the most widely used. It seems that it is this scale is least aﬀected by somatic disorders and handicaps. It consists of 20 items. The validity of the CES-D might be compromised when used with somatic patients or elderly individuals, and modifications for its use in this population has been recommended. • Young Mania Rating Scale (YMRS) (Young, Biggs, Ziegler, & Meyer, 1978): The YMRS is an 11-item scale used to assess the severity of mania in patients with a diagnosis of bipolar disorder. It takes 15-30 minutes to complete by a trained examiner. It is a reliable easy to use and simple tool, widely used. Some 4 items have double-rating which can lead to questions of reliability. • The Bech-Rafaelsen Mania Rating Scale (MRS) (Bech, Rafaelsen, Kramp, & Bolwig, 1978): It consists of 11 items and assesses the severity of mania in bipolar patients. It is rated by an examiner. • General Assessment of Functioning) (GAF): This is a scale introduced by the DSM classification system, that assesses global functioning in the psychological, family, social and occupational spheres and attempts to localize it on a continuum from 0 (full decline of functioning, the patient is dangerous to self or others) to 100 (supreme level of functioning). It shares many characteristics with the visual analog scale, and represents a non-specific way to quantify everyday functioning, but with low reliability and accuracy. • General Assessment of Relational Functioning (GARF): It can be used to assess the patient’s family or the general environment in which he/she lives. • Social and Occupational Functioning Assessment Scale (SOFAS): This is a scale for the assessment of functioning in work place and in social situations. Both GARF and SOFAS are introduced by DSM-IV, and share characteristics with GAF. Their major diﬀerence is that they have a restricted field of functioning to assess. • Clinical Global Impression (CGI): This is a group of simple scales assessing symptom severity, treatment response and the eﬃcacy of treatments in treatment studies of patients with mental disorders. They include the Clinical Global Impression - Severity scale (CGI-S) which is a 7-point scale, the Clinical Global Impression - Improvement scale (CGI-I) which is a 7 point scale and the Clinical Global Impression - Eﬃcacy Index which is a 4 point X 4 point rating scale • TEMPS-A (Akiskal, Akiskal, Haykal, Manning, & Connor, 2005), NEO-PI (Costa & McCrae, 1997), TCI (Cloninger, Svrakic, & Przybeck, 1993) and the MMPI-2 (Butcher, Graham, & Fowler, 1991): They are self-report questionnaires that assess temperament, character and personality The literature suggests there is no significant diﬀerence among the various self-administered instruments assessing depression in terms of performance and overall sensitivity is around 84% and specificity around 72% (Fountoulakis, Bech et al. 2007; Mulrow et al. 1995). Neuropsychological Tools The assessment of neurocognitive function is very important especially for psychogeriatric patients even in cases without observable symptoms or signs of "organic" disorder or dementia. Scales for rapid screening of cognitive disorder are the following: • Mini Mental Status Exam-(MMSE) (Folstein, Folstein, & McHugh, 1975): It is a brief mental status examination designed to quantify cognitive status by assessing performance on the following cognitive domains: orientation, language, calculation, memory and visuospatial reproduction thus providing a brief measure of global cognitive functioning. • The Cambridge Cognitive Examination For The Elderly-(CAMDEX) (Roth et al. 1986): It includes a large number of items covering almost every aspect of the patient's medical history as well as his/her family medical history. It also includes evaluation of the patients’ current condition concerning both physical and mental health. Sixty-eight of these items constitute the CAMCOG scale, which is the part of CAMDEX examining the patient's cognitive functions. The MMSE score is simultaneously obtained. CAMCOG includes eleven subscales. Each one evaluates a "diﬀerent" cognitive function of the patient: Orientation, Language/Comprehension, Language/Expression, Remote Memory, Recent Memory, Learning, Attention, Praxis, Calculations, Abstract Thinking and Perception. • Weschler Memory Scale-Revised (D'Elia, Satz, & Schretlen, 1989) Maybe the most global and comprehensive scale for the assessment of memory. Its greatest drawback is that it is time consuming. It includes testing of Personal and current information, Orientation, Mental Control, Logical Memory, Digits forward and backward, Visual reproduction and Associated learning. • Weschler Adult Intelligence Scale - Revised (WAIS-R): The WAIS-R gives a global Intelligence Quotient (IQ) and also two subscales: verbal and performance. • Clock Drawing Test (Sunderland et al. 1989): This is a simple test which demands the patient to draw a clock. It can be used as a screening tool especially for dementia. The test requires multiple cognitive functions to co-operate. • Verbal Fluency Test : The test demands the patient to name as many objects and animals is able to within a time frame of 1 minute. • Trail Making Test (Reitan, 1971): The first form of is test demands the patient to trail the sequence of numbers put at random places on paper by using a pencil, while the second form demands to alternate between numbers and letters randomly put on paper. The time needed to fulfill each of the two tasks is recorded. The test is an assessment of general mental function.